ALLOGRAFT AND XENOGRAFT UNRESPONSIVENESS INDUCED BY TRANSPLANTATION OF NEONATAL SKIN

Class I MHC-disparate skin allografts from neonatal donors survive lon ger than adult grafts in mice treated with antilymphocyte serum (ALS; days -1, +2) or ALS plus donor bone marrow cells (BMC; day +7 relative to grafting on day 0) or ALS, BMC, and a 2-week course of post-transp lant CsA. We have now investigated whether this phenomenon extends to more strongly histoincompatible allografts (H2-KI and H2-KID mismatche d) made to recipients treated with ALS, ALS plus BMC, or ALS, BMC, and CsA. Survival of neonatal grafts was longer than that of adult grafts in all experimental groups (P<0.05). In ALS/BMC/CsA-treated mice, for example, median survival of neonatal C3H grafts was 46 days, with adu lt grafts surviving 22 days on C57BL/6 recipients (full MHC disparity) . Survival of neonatal hamster skin grafted to B6AF1 mice was not augm ented beyond that for adult skin using a similar immunosuppressive pro tocol. But if alternate day ALS and CsA injections were begun on day - 5, and ALS and CsA continued as in the allograft models, a significant xenogeneic neonatal survival advantage was demonstrated. (Donor BMC h ad no graft-prolonging effect in the xenograft model.) Donor BMC signi ficantly prolonged full MHC-mismatched grafts from newborn, but not ad ult donors in ALS-treated recipients. Also, addition of CsA to ALS/BMC treatment prolonged the survival of neonatal, but not adult grafts mi smatched at KI or KID. These results indicate that the survival advant age of neonatal grafts in immunosuppressed recipients extends to stron g allogeneic incompatibilities and even to a xenograft model.